6B.1 Non-Specific Immune Responses to Infection PDF

# 6B.1 - Non-Specific Responses to Infection ## Cell Recognition * The body's ability to recognize "self" and "non-self" cells is the main reason why you are not always sick, as the body stops the invasion and destroys the pathogen. * Cells of different organisms have genetically determined protei...

# 6B.1 - Non-Specific Responses to Infection ## Cell Recognition * The body's ability to recognize "self" and "non-self" cells is the main reason why you are not always sick, as the body stops the invasion and destroys the pathogen. * Cells of different organisms have genetically determined proteins which are essential for recognition, such as _glycoproteins_ in the bilayer of the cell membrane. * Recognizing self and non-self cells is equally important, and non-self glycoproteins usually act as _antigens_ which are recognized by white blood cells during specific immune responses, which stimulate the immune response. * Antigens can range from being proteins to being toxins made by whole microorganisms. * _Leukocytes_ can have non-specific responses to any type of pathogen, and specific responses to certain types of pathogens. ## Leukocytes & Their Types * Formed in the bone marrow, they have the responsibility of defending the body against infection. * Although much larger than erythrocytes, leukocytes can squeeze themselves through tiny blood vessels, as they can change their shape. * Some contain granules in their cytoplasm, while others do not, and leukocytes have many types. ## Granulocytes * Granulocytes are leukocytes with granules, involved in non-specific responses, have lobed nuclei, and consist of 3 different types: * **Neutrophils**: engulf and digest pathogens by phagocytosis, and make up to 70% of leukocytes. * **Eosinophils**: fight against parasites, and are involved in allergic reactions, inflammation, and in developing immunity to diseases. * **Basophils**: produce histamines and are involved in inflammation and allergic reactions. ## Agranulocytes * Agranulocytes are leukocytes without granules, involved in specific responses, and have round nuclei. * They consist of two types: * **Monocytes**: which are a type of white blood cell that is present in the blood of mammals and is a precursor to tissue macrophages. They pass from the blood to the tissues to form cells called _macrophages_ which engulf and destroy pathogens by phagocytosis. * **Lymphocytes**: are small leukocytes. ## Non-Specific Responses * **Inflammation** - This is a non-specific response which usually happens in the case of localized infection. * To begin with, _mast cells_ found at the surface of the cell will release chemicals called _histamines_ which cause the blood vessels in the area to dilate, leading to localized heat and redness, reducing the reproduction rate of pathogens. * This also forces cells forming the walls of the capillaries to separate, making the capillaries more permeable, releasing plasma containing leukocytes and forcing antibodies out of the body, disabling pathogens and allowing phagocytosis to occur. * **Fevers** - This is a non-specific response to infection where the hypothalamus resets the body temperature to one that is higher, for two reasons: * Many pathogens reproduce quickly at 37°C and below, so a higher temperature will reduce their ability to effectively reproduce. * Specific immune responses function better at higher temperatures, making combat against infection more successful. * Although raising temperature is beneficial, it can be fatal if not treated correctly. * Due to the increase, the patient will start to sweat to cool the body down, releasing fluid and electrolytes. * If not replaced, this could lead to severe dehydration. * Moreover, it could cause enzymes to denature, resulting in permanent tissue damage. * **Phagocytosis** - This is the use of _lysozymes_ found in _lysosomes_ to break down and digest pathogens. * Using _neutrophils_, which digest a few pathogens and die as they can't renew lysosomes, and _macrophages_, which can digest many pathogens as they can renew the lysosomes, and will accumulate at the site of infection. * Afterwards, the pathogen will be encased in a _phagosome_ which will be seen as pus coming out of a wound or being reabsorbed into the body. * Lastly, _cytokines_ which stimulate other phagocytes to move to the site of infection and raise body temperature, are also released. * **Interferons** - Cells which are invaded by viruses will release a group of chemicals called _interferons_ which inhibit viral replication within the cell, and diffuses to other cells to make them resistant to infection, making the virus unable to further reproduce. # 6B.2 - The Specific Response to Infection * The specific response recognizes "non-self" invaders through their _antigens_ which are unique markers they carry. * The immune system is very diverse, and grants immunological memory, but the main types of leukocytes involved are _lymphocytes_ and _macrophages_. ## The Main Types of Lymphocytes * **B-cells**: produced in the bone marrow, have globular receptor proteins used in producing _immunoglobulins_ (antibodies). * They have the potential to recognize and deal with a large deal of pathogens. * When bound to antigens, produce: * **B-effector cells** - divide to form plasma clones * **Plasma cells** - produce antigen-specific antibodies. * **B-memory cells** - provide immunological memory * **T-cells**: produced in the bone marrow and activated in the thymus gland, display several identical _T-cell receptors_ which bind to antigens to produce: * **T-killer cells** - produce chemicals to destroy infected cells. * **T-helper cells** - activate plasma cells to produce "antigen-specific" antibodies and secrete _opsonins_ to label pathogens for phagocytosis * **T-memory cells** - very long-lived cells that make up part of the immunological memory. * **Major Histocompatibility Complexes (MHC)** are responsible for many of the workings of the cells. ## The Humoral Response * This response mainly reacts to antigens which aren't found in the body cells, as well as _antigen-presenting cells (APC)_. * This response will produce antibodies through the two main stages: * **T helper activation stage**: When pathogens enter, they release chemicals which attract _phagocytes_. * Whereas neutrophils engulf pathogens in 10 minutes, _macrophages_ take longer, but prepare the way for the specific response. * The macrophage separates the antigen and combines it with an _MHC_. * The macrophage displays the complex on its outer membrane, and is known as an _antigen-presenting cell (APC)_. * Afterwards, receptors on the T-cells bind to the specific antigen on the antigen-MHC complex of the APC to form clones of mainly active _T-helper cells_ and some _T-memory cells_ that grant immunological memory. * **Effector stage**: The immunoglobulins of B-cells bind to the antigen presented by the pathogen, causing the cell to engulf and destroy it, by lysosomes. Fragments of the pathogen's antigen fuse with the MHC protein within the cell to form a complex that is presented on the outer membrane of the cell. * An active T-helper cell from the previous stage binds to the MHC antigen on the MHC complex as it recognizes it, and releases _cytokines_ which stimulate B-cells to divide to form clones of B-effector cells (which differentiate to form plasma cells) and B-memory cells (which grant immunological memory). ## The Cell-Mediated Response * In this case, the pathogen infects a body cell, causing the humoral response to be ineffective, mainly occurring in viral infections. * _T-killer cells_ will respond. * After the body cell is infected, it will digest the pathogen, and its antigens become bound to the MHC. * This complex is presented on the outer membrane, as such, the cell ultimately becomes an APC, but is still infected. * This causes T-killer cells to react and bind their complementary receptor to the antigen on the MHC. * This exposes them to cytokines from previously activated T-helper cells, triggering a series of rapid cell division. * The T-killer cells will release enzymes into the infected cell, which forms pores. * Causing it to rupture. * Any undamaged antigens will be labeled by antibodies and later destroyed. ## Primary and Secondary Immune Response * The first time the body is infected, antibodies are produced by plasma cells, and this could take very long, which is why symptoms develop. * However, if the same pathogen invades again, a secondary response is triggered, which is greater and longer-lasting. * When B-cell APCs divide, they produce B-memory cells which recognize antibodies from previous invaders and help quickly produce antibodies so that the pathogen is quickly destroyed before symptoms develop. * Moreover, when T-killer cells are cloned, they form T-memory cells, which release a large number of T-killer cells to destroy infected cells quickly if the same pathogen attacks. * All of this forms an immunological memory. # 6B.3 - Developing Immunity * Once you encounter a disease, you will probably not encounter it one more time, as you develop immunity due to immunological memory. ## Types of Immunity * There are two main types of immunity, each with their passive and active form, which are: * **Natural immunity**: * This happens through the normal course of an organism's life, rather than through medication. * **Natural active immunity**: This is when your body comes into contact with a foreign antigen, causing the immune system to be activated to produce antibodies against the pathogen, to destroy it. * **Natural passive immunity**: This is temporary immunity given from the mother to the fetus, through the transfer of pre-formed antibodies through the placenta or the mother's milk, and this lasts until the fetus immune system becomes active. * **Artificial immunity**: * This is a main way of granting immunity through _immunisation_ by vaccines, which exposes the body to a safe form of a specific antigen. * **Artificial passive immunity**: Where antibodies from one individual are extracted and injected in another, which prevents development of the disease, but not give long-term immunity. * Referred to as _artificially acquired passive immunity_. * **Artificial active immunity**: * Small amounts of a safe form of the pathogen are used to grant immunity, in one of four ways: * Injection of detoxified form of toxin * Inactivated viruses or dead bacteria * Attenuated pathogens * Using fragments of outer coats of viruses ## Eradication, Elimination, and Control of Disease * There are three ways of reducing the effect of diseases, which are: * **Eradication of disease**: This is when a disease is not found in either people, animals, or anywhere in the environment. * **Elimination of disease**: This is when eradication is not realistically possible, and so the disease disappears in defined but the pathogen remains in animals, the environment, or in mild infections which are not recognized, so immunization must continue regardless of the number of cases. * **Control of disease**: In most cases, the disease evolves too quickly to make a medicine or vaccine. * As quickly as the target pathogen evolves too. * Quickly as the surface of the pathogen's antigens evolves too quickly. ## Herd Immunity * This is when a large portion of the population is vaccinated against a disease, so that it becomes very difficult for the disease to keep affecting the population. * It is important that anyone who can be vaccinated is vaccinated, so that those cannot be vaccinated do not catch the disease. * It is important to provide _herd immunity_ when there is a serious outbreak of a disease. # 6.B.4 - Antibiotics: Treating Bacterial Disease ## Drugs Against Microorganisms * _Antibiotics_ destroy microorganisms or prevent them from reproducing. * Along with immunization, this has cured many diseases. * Antibiotics work based on _selective toxicity_ by interfering with the chemistry or metabolism of the bacteria, without affecting the human host. ## Antibiotic Action * Antibiotics consist of two main types, which are: * **Bacteriostatic**: In this case, the antibiotic completely inhibits the growth of the microorganisms, and have two main antimicrobial actions: * Interrupts metabolic pathways to block nucleic acid or viral nutrient synthesis. * Protein synthesis inhibition or prevention of transcription and translation of microbial genes. * **Bactericidal**: Here, almost all pathogens are used, and this is mainly used in cases where there is serious infection, which has three main antimicrobial actions: * Prevent formation of _cross-linking_ cell walls to kill bacteria by lysis. * Damage the cell membrane so water moves in or metabolites move out, killig the bacteria. * Stop bacterial DNA winding into rings, so that it can no longer fit inside the cell. ## Broad-Spectrum and Narrow-Spectrum Antibiotics * Whereas _broad-spectrum antibiotics_ destroy a wide range of bacteria, _narrow-spectrum antibiotics_ target one or two pathogens. * There are many factors that go into the effectiveness of antibiotics, which are: * Concentration of drug around infected area. * Local pH. * Whether the pathogen or host cell destroy the antibiotic. * Susceptibility of pathogen to the antibiotic used. * If a high dosage of the antibiotic is needed, the pathogen is said to be _moderately sensitive_, but if an average dosage is used, then the pathogen is said to be _sensitive_. * Sometimes, the pathogen becomes _resistant_ to the antibiotic that was originally used. * Then, it is said to be _antibiotic resistant_. # 6B.5 - Antibiotic Resistance ## Antibiotic/Drug-Resistant Bacteria * There is a constant evolutionary race between drugs and bacteria. * In order for the drug to be effective, bacteria have to have a binding site and a metabolic reaction or pathway which the drug interrupts. * However, mutations during reproduction have helped bacteria grow resistant to antibiotics. * By the rules of natural selection, the mutations are passed on. * This is because patients have been taking many antibiotics to cure diseases, which increases selection pressures and leads to the creation of "superbugs". * To reduce selection pressures, we should: * Use antibiotics only when strictly necessary. * Make sure people complete their antibiotic course. * Using as few different antibiotics as possible and introduce newer bacteria antibiotics when possible ## Hospital-Acquired Infections (HAIs) * _Clostridium difficile_ and _methicillin-resistant Staphylococcus aureus (MRSA)_ are two very common HAIs, and each has its own problems and methods of infection, shown on the next page. * **MRSA:** * _S.aureus_ can be on the skin or inside nasal passages without affecting us, but once inside the body, it can have negative effects. * Usually treated with methicillin, but has now developed resistance to it. * Currently, these infections can only be treated using very high dosages, but this might lead to the evolutionary problem once more. * **Clostridium Difficile:** * This is an anaerobic bacteria which can be present in the body and not cause harm, as the are limited in numbers. * However, taking antibiotics to kill other bacteria may result in killing the gut flora, which can cause _Clostridium difficile_ to rapidly reproduce and release harmful toxins. ## Infection Prevention and Control * As of now, codes of practice have been set, as well as other measurements to reduce HAIs, which are: * **Controlling the use of antibiotics**: Antibiotics should be used carefully, only when necessary, and the full course has to be completed. * If not completed, the immune system will not be able to destroy all the bacteria, and so they can infect other people and grow resistant. * In addition, the use of many antibiotics will also encourage the bacteria to evolve. * **Hospital practice**: Hospitals have placed many specific codes of practice to help prevent HAIs, which are: * **Hand-washing / Hygiene practice**: In between sessions, doctors and nurses should always wash their hand with alcohol-based gels and chlorine-disinfectants, to destroy any pathogens. * In addition, they should wear appropriate clothing as to not spread pathogens. * Lastly, hospital wards, toilets, and equipment should be thoroughly cleaned. * **Isolation of patients**: HAI infected patients need to be isolated in high-level hygiene and disinfectant rooms, as to prevent the spread of the infection. * **Prevention of infection coming into the hospital**: Patients carrying communicable diseases need to be treated of them first before they are treated of the main infection. * As to not spread infection. * Moreover, unwell people should not visit patients, and when visiting, visitors should maintain a high level of hygiene. * **Monitoring levels of HAIs**: Measuring and reporting is important as it attracts attention so that more efforts are put in to solve the problem.